Identification of oxidative degradation impurities of Olanzapine drug substance as well as drug product

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 56; no. 2; pp. 413 - 418
• Main Authors: Rao, P. Sreenivasa, Ray, Uttam Kumar, Hiriyanna, S.G., Rao, Sumathi V., Sharma, Hemant Kumar, Handa, Vijay Kumar, Mukkanti, K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.09.2011; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antipsychotic Agents - analysis; Antipsychotic Agents - chemistry; antipsychotics; Benzodiazepines - analysis; Benzodiazepines - chemistry; Biological and medical sciences; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; degradation; Drug Contamination; Drug Stability; Excipients - analysis; Fundamental and applied biological sciences. Psychology; General pharmacology; Impurities; Isolation; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Olanzapine; Oxidation-Reduction; Oxidative degradation; oxidative stability; pharmacology; Pharmacology. Drug treatments; Structure elucidation; Tablets; Tandem Mass Spectrometry; Technology, Pharmaceutical - methods; Isolation; Olanzapine; Impurities; Structure elucidation; Oxidative degradation; Drug; Dibenzodiazepine derivatives; Atypical antipsychotic; Impurity; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Serotonine receptor; Thienobenzodiazepine derivatives; D2 Dopamine receptor; Active ingredient; Qualitative analysis; Structural analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.05.003

Impurities found in stressed and stability studies of Olanzapine (polymorphic form-I) [1–7] in both drug substance and drug product are described. These impurities are identified as 4-(4-methyl-1-piperazinyl)-3-hydroxymethylidene-1 H-benzo[b][1,4]diazepine-2(3H)-thione (hydroxymethylidene thione) and (Z)-4-(4-methyl-1-piperazinyl)-3-acetoxymethylidene-1 H-benzo[b][1,4]diazapine-2(3H)-thione (acetoxymethylidene thione). An oxidative degradation pathway of Olanzapine, for the formation of these impurities, has been proposed.